High-resolution x-ray measurements of the electron density distribution (EDD) and the molecular electrostatic potential (MEP) for some tricyclic antidepressant and butyrophenone type drugs used to treat the symptoms of psychosis, will be collected. Until recently, these properties could only be obtained from theoretical calculation. With the recent development of experimental x-ray methods, it is now possible to obtain from the same experiment, not only the shape of the drug molecule, but also the EDD and MEP, which may be used to predict relative reactivities. Studies of other biological model compounds show that these electronic factors are now measurable with an accuracy at least equivalent to the best calculations on small molecules. Initially a selected set of substituted phenothiazines and two other tricyclic antidepressants that range in activity from strong antipsychotic drugs to drugs with little or no antipsychotic activity (fluphenazine, triflupromazine, promethazine, alpha- chlorprothixene and imipramine) have been chsoen for study. Also, Haloperidol, a very potent neuroleptic; and Droperidol, a butyrophenone with tranquilizing properties, will be studied. These studies will be used to identify EDD and of MEP trends that may be used to predict relative reactivities. Information will also be available concerning both the stereochemical and electronic requirements of the dopamine receptor site and to attempt to understand how such small structural modifications may result in radical differences in antipsychotic activity.